leukotoxin and Arthritis--Rheumatoid

Leukotoxin A (LtxA) is the major virulence factor of an oral bacterium known as

Topics: Aggregatibacter actinomycetemcomitans; Anti-Citrullinated Protein Antibodies; Arthritis, Rheumatoid; Exotoxins; Humans; Pasteurellaceae Infections

A relationship between rheumatoid arthritis (RA) and periodontitis has been suggested from findings that individuals with RA are prone to have advanced periodontitis and vice versa. In search of possible common pathogenetic features of these two diseases, we investigated the presence of citrullinated proteins and expression of endogenous peptidylarginine deiminases (PAD2 and PAD4), in periodontal tissue of individuals with periodontitis and healthy controls, in relation to the periodontal pathogens Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), producing leukotoxin as virulence factor. These two oral bacteria have been suggested to be linked to anti-citrullinated protein antibodies in patients with RA.. Gingival tissue biopsies were obtained from 15 patients with periodontitis and 15 individuals without periodontal disease. Presence of CD3-positive lymphocytes, citrullinated proteins, PAD2, PAD4, P. gingivalis as well as A. actinomycetemcomitans and Mannheimia haemolytica produced leukotoxins were analysed by immunohistochemistry, followed by triple-blind semi-quantitative analysis. Mann-Whitney and Fisher's exact tests were used to analyse differences between groups. PADI2 and PADI4 mRNA levels were assessed by RT-qPCR and analysed using Wilcoxon signed rank test.. Increased staining of citrullinated proteins was observed in gingival connective tissue from subjects with periodontitis (80%, 12/15) compared to healthy gingival tissue (27%, 4/15), whereas no differences were observed in gingival epithelium. There was also an increased staining of the citrullinating enzymes PAD2 and PAD4 in gingival connective tissue of patients with periodontitis whereas similar levels of PAD2 and PAD4 were observed in the gingival epithelium of the two groups. Similarly, the mRNA levels of PADI2 and PADI4 were also increased in the gingival tissue of patients with periodontitis compared to healthy controls. Furthermore, presence of P. gingivalis and leukotoxins was comparable in both epithelium and connective tissue, from the different investigated individuals with and without periodontitis, and there were no correlations between the presence of periodontal pathogens and the expression of citrullinated proteins or PAD enzymes.. Chronic gingival inflammation is associated with increased local citrullination and PAD2 and PAD4 expression in periodontitis. The increased citrullination and PAD2 and PAD4 expression in periodontitis were, however, independent of the presence of periodontal pathogen P. gingivalis and A. actinomycetemcomitans leukotoxin.

Topics: Adult; Aggregatibacter actinomycetemcomitans; Arthritis, Rheumatoid; Citrullination; Exotoxins; Gingiva; Humans; Inflammation; Lymphocytes; Middle Aged; Periodontitis; Porphyromonas gingivalis; Protein-Arginine Deiminases; RNA, Messenger

A soluble extract from Actinobacillus actinomycetemcomitans (designated strain Y4) caused dose-dependent cytotoxic changes in PMN isolated from the gingival crevices (C-PMN) of normal adults. When the toxin was preincubated with sera from patients with juvenile periodontitis, there was a significant inhibition of toxic activity. In contrast a variety of other sera from normal subjects with healthy gingiva, and from patients with chronic gingivitis, chronic periodontitis, recurrent herpes labialis, rheumatoid arthritis, or ulcerative colitis enhanced the leukotoxic activity. The neutralization of toxin by serum from patients with juvenile periodontitis was probably due to specific antibodies. Since Actinobacillus actinomycetemcomitans organisms can be frequently identified in subgingival plaque from patients with juvenile periodontitis, the capacity of Y4 toxin to kill C-PMN may contribute to the pathogenesis of this disease.

Topics: Actinobacillus Infections; Adult; Animals; Arthritis, Rheumatoid; Chronic Disease; Colitis, Ulcerative; Crohn Disease; Culture Media; Exotoxins; Gingival Diseases; Herpes Labialis; Humans; Neutralization Tests; Neutrophils; Periodontitis; Rabbits